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Childhood obesity is an established health problem, and there is a growing need for health promotion interventions focused on healthy behaviors in collaboration with parents and schools. The Mediterranean diet (MD) could help to tackle obesity, but it is essential to maintain a good level of physical activity (PA) and limit time spent in sedentary activities (ST). To explore family determinants, adherence to the MD and PA levels as potential predictors of a child’s health-related behaviors, we performed a cross-sectional analysis of 368 Italian primary school children with a mean age of 8.95 years (SD = 1.43). Data were collected from May to June 2017 using a weekly diary, an interactive tool to assess the child’s and parents’ lifestyle. The child’s degree of adherence to the MD was calculated using the KIDMED index. Adherence to the MD was high, medium and poor in 5.2%, 62.5% and 32.3% of children, respectively. Higher maternal educational level was positively associated with children’s MD and PA (p < 0.05) and negatively correlated to ST. Maternal fruit and vegetable consumption was positively related to the MD and negatively related to ST (p < 0.05). Maternal PA was positively associated with the MD (p < 0.001). Paternal PA, and fruit and vegetable consumption, were positively associated with children’s PA (p < 0.05). Our results underline the need for future studies, mainly focused on school-based and family-based interventions, to promote healthy lifestyles and nutritional habits.

Background Spindle cell oncocytomas are extremely rare neoplasms of the sellar, parasellar, and suprasellar regions that can frequently mimic pituitary adenomas. Fewer than 50 cases have been ever reported in the literature, and there is no consensus on best treatments to be provided. Case Description We hereby present a challenging case of sellar and suprasellar spindle cell oncocytoma in a patient of 64 years. The patient, who presented with hydrocephalus, hypopituitarism, and visual deficit, underwent urgent transsphenoidal (TNS) resection of the mass, which was aborted for massive life-threatening bleeding. The patient received ventriculoperitoneal shunt with relief of symptoms. An endovascular embolization of tumor feeders from the distal portion of the right internal maxillary artery, in particular the sphenopalatine artery, was then performed and a second-look TNS surgery was feasible. The patient was discharged in optimal clinical condition, recovered both endocrinologic and visual deficits, and is now in follow-up. Conclusions We found that the oncocytoma was radiologically and clinically comparable with a pituitary adenoma, except for higher representation of vasculature. According to our recent experience and review of the literature, we believe that surgery (transsphenoidal or transcranial approach) is the recommended treatment in those who are symptomatic and preoperative embolization might be a suitable option to reduce intraoperative bleeding and increase radicality.

Preparedness for the ongoing coronavirus disease 2019 (COVID-19) and its spread in Italy called for setting up of adequately equipped and dedicated health facilities to manage sick patients while protecting healthcare workers, uninfected patients, and the community. In our country, in a short time span, the demand for critical care beds exceeded supply. A new sequestered hospital completely dedicated to intensive care (IC) for isolated COVID-19 patients needed to be designed, constructed, and deployed. Along with this new initiative, the new concept of "Pandemic Radiology Unit" was implemented as a practical solution to the emerging crisis, born out of a critical and urgent acute need. The present article describes logistics, planning, and practical design issues for such a pandemic radiology and critical care unit (e.g., space, infection control, safety of healthcare workers, etc.) adopted in the IC Hospital Unit for the care and management of COVID-19 patients.

A large body of literature has demonstrated that the mechanical properties of microenvironment have a key role in regulating cancer cell adhesion, motility, and invasion. In this work, we have introduced two additional parameters, named cell trajectory extension and area traveled by cell, to describe the tendency of normal tissue and metastatic cancer cells to move in a directional way when they interact with physio-pathological substrates, characterized by stiffnesses of 1–13 kPa, before and after treatment with 2 doses of X-rays (2 and 10 Gy). We interpreted these data by evaluating also the impact of substrate stiffness on 2 morphological parameters which indicate not only the state of cell adhesion, but also cell polarization, prerequisite to directional movement, and the formation of protrusions over cell perimeters. We believe that a so wide analysis can give an efficient and easily readable overview of effects of radiation therapy on cell-ECM crosstalk when used as therapeutic agent.

Cutaneous melanoma is a lethal disease, even when diagnosed in advanced stages. Although recent progress in biology and treatment has dramatically improved survival rates, new therapeutic approaches are still needed. Deregulation of epigenetics, which mainly controls DNA methylation status and chromatin remodeling, is implied not only in cancer initiation and progression, but also in resistance to antitumor drugs. Epigenetics in melanoma has been studied recently in both melanoma preclinical models and patient samples, highlighting its potential role in different phases of melanomagenesis, as well as in resistance to approved drugs such as immune checkpoint inhibitors and MAPK inhibitors. This review summarizes what is currently known about epigenetics in melanoma and dwells on the recognized and potential new targets for testing epigenetic drugs, alone or together with other agents, in advanced melanoma patients.

Objectives: To determine interobserver variability in axillary nodal contouring in breast cancer (BC) radiotherapy (RT) by comparing the clinical target volume of participating single centres (SC-CTV) with a gold-standard CTV (GS-CTV). Methods: The GS-CTV of three patients (P1, P2, P3) with increasing complexity was created in DICOM format from the median contour of axillary CTVs drawn by BC experts, validated using the simultaneous truth and performance-level estimation and peer-reviewed. GS-CTVs were compared with the correspondent SC-CTVs drawn by radiation oncologists, using validated metrics and a total score (TS) integrating all of them. Results: Eighteen RT centres participated in the study. Comparative analyses revealed that, on average, the SC-CTVs were smaller than GS-CTV for P1 and P2 (by −29.25% and −27.83%, respectively) and larger for P3 (by +12.53%). The mean Jaccard index was greater for P1 and P2 compared to P3, but the overlap extent value was around 0.50 or less. Regarding nodal levels, L4 showed the highest concordance with the GS. In the intra-patient comparison, L2 and L3 achieved lower TS than L4. Nodal levels showed discrepancy with GS, which was not statistically significant for P1, and negligible for P2, while P3 had the worst agreement. DICE similarity coefficient did not exceed the minimum threshold for agreement of 0.70 in all the measurements. Conclusions: Substantial differences were observed between SC- and GS-CTV, especially for P3 with altered arm setup. L2 and L3 were the most critical levels. The study highlighted these key points to address. Advances in knowledge The present study compares, by means of validated geometric indexes, manual segmentations of axillary lymph nodes in breast cancer from different observers and different institutions made on radiotherapy planning CT images. Assessing such variability is of paramount importance, as geometric uncertainties might lead to incorrect dosimetry and compromise oncological outcome.

Squamous cell carcinoma of the anus (SCCA) is a rising health issue, strongly related to other relevant medical conditions such as (HIV) and human papillomavirus (HPV) infection. Correct assessment of patients with SCCA requires a multidisciplinary evaluation and adequate follow-up. Accurate local and systemic staging, as well as risk evaluation, are essential to optimal treatment planning. Early stage tumours can be definitively treated with a combination of chemotherapy and radiotherapy, while salvage surgery is usually reserved for patients who develop local recurrence. Distant recurrence and de novo metastatic disease are associated with poorer prognosis and require palliative systemic chemotherapy, with different single agent and combination options available. Finally, recent discoveries on the carcinogenesis of SCCA have allowed the development of innovative treatment options, the most promising being immune checkpoint inhibitors. The limited systemic treatments for SCCA and low incidence of the disease, together with insufficient data from clinical research could explain the poor outcomes of these patients, which should therefore be managed in high volume centres and enrolled in clinical trials whenever possible. This article summarises the main strategies for treating patients with SCCA.

Tumor heterogeneity represents a possible cause of error in detecting predictive genetic alterations on tumor tissue and can be overcome by testing alterations in circulating tumor DNA (ctDNA) using liquid biopsy. We assessed 72 consecutive patients with a diagnosis of metastatic colorectal cancer (mCRC) using Idylla&trade, Biocartis, a fully automated platform that evaluates the most frequent mutations of KRAS, NRAS and BRAF genes. We correlated the results of liquid biopsy and standard tissue-based next generation sequencing (NGS) analyses to patient clinical features. The overall agreement was 81.94%. Concordance was 85.71% and 96.15% in treatment-na&iuml, ve patients and in the patient subgroup with liver metastases, respectively. In liver metastases positive, treatment-na&iuml, ve patients, sensitivity, specificity and positive predictive value (PPV) were 92.31%, 100% and 100%, respectively. Circulating mutational fraction (CMF) was significantly higher in patients with liver metastases and high carcinoembryonic antigen (CEA) levels. In a subgroup of patients pre-treated with anti-Epidermal Growth Factor Receptor (EGFR) agents, emerging KRAS mutations were evidenced in 33% of cases. Testing RAS/BRAF mutations on plasma using the Idylla&trade, Biocartis platform is feasible and reliable in mCRC patients in clinical practice.

This report aims to illustrate how to perform a venous access to a COVID-19 patient at the bedside. The decision on the type of venous access, the selection of the material necessary to perform the procedure, and the preparation of the operators are described. The described approach can reduce costs, speed up execution times, and make the operator’s work safer. Furthermore, these precautions may help control the spread of COVID-19 within the healthcare facility.

BACKGROUND. Aim of the study is to evaluate the incidence of DVT in COVID-19 patients and its correlation with the severity of the disease and with clinical and laboratory findings.METHODS. 234 symptomatic patients with COVID-19, diagnosed according to the World Health Organization guidelines, were included in the study. The severity of the disease was classified as moderate, severe and critical. Doppler ultrasound (DUS) was performed in all patients. DUS findings, clinical, laboratory’s and therapeutic variables were investigated by contingency tables, Pearson chi square test and by Student T test and Fisher's exact test. ROC curve analysis was applied to study significant continuous variables.RESULTS. Overall incidence of DVT was 10.7% (25/234): 1.6% (1/60) among moderate cases, 13.8% (24/174) in severely and critically ill patients. Prolonged bedrest and intensive care unit admission were significantly associated with the presence of DVT (19.7%). Fraction of inspired oxygen, P/F ratio, respiratory rate, heparin administration, D-dimer, IL-6, ferritin and CRP showed correlation with DVT. CONCLUSIONS. DUS may be considered a useful and valid tool for early identification of DVT. In less severely affected patients, DUS as screening of DVT might be unnecessary. High rate of DVT found in severe patients and its correlation with respiratory parameters and some significant laboratory findings suggests that these can be used as a screening tool for patients who should be getting DUS.

The COVID-19 pandemic has deeply impacted the activity of interventional oncology in cancer centers. Since the first COVID case was diagnosed in Italy on February 21st, our Hospital, located in Milan downtown, has been at the frontline to manage this emergency and to try to ensure essential services. In the present article, we discuss the changes that need to be done for the organization, safety, and patient management in interventional oncology.

Immunotherapy has recently become a major treatment modality for several types of solid tumours, achieving remarkable and long-lasting remissions. In metastatic colorectal cancer patients (mCRC), immune checkpoint inhibitors (ICIs) were found to be effective as treatment for deficient mismatch repair (dMMR)/ microsatellite instability high (MSI-H) tumours and received regulatory approval for this indication. However, mCRC is a complex disease and dMMR/MSI-H tumours represent a minority of the cases; therefore, new strategies are needed to extend the benefits of immunotherapy to a larger population of patients. This review explores the immunological differences between dMMR/MSI-H and proficient mismatch repair (pMMR)/ microsatellite instability low (MSI-L) tumours, focuses on new proposed biomarkers to predict response to immunotherapy and illustrates results reported from the main clinical trials with immunotherapeutic agents in CRC, addressing the most promising approaches being currently developed.

This is an illustrated case about CT ventilation and perfusion in Covid patient.

Selective embolization is the treatment of choice for traumatic renal pseudoaneurysm. The use of ethylene vinyl alcohol copolymer (EVOH) was recently described as an embolic agent in peripheral lesions. The aim of a good embolic agent is to: achieve rapid and effective embolization; reach and fill distal vasculature targeted for embolization; be easy to prepare and use. Moreover, it should be highly radiopaque, controllable during administration, biocompatible and cost-effective. EVOH is a non-adhesive embolic agent and its efficacy is independent from the coagulant status. The risk of non-targeted embolization should be reduced by the good radio-opacity of the embolic material that is injected under continuous fluoroscopy. Nevertheless, symptomatic EVOH migration was described. We report a unique case of embolization of a renal pseudoaneurysm and migration of EVOH in the urinary tract. Retrograde trans-urethral removal of the migrated embolic agent was successfully performed. Our case report indicates that EVOH may not be appropriate when a fistula with renal calyx is suspected, even if its migration in the urinary tract may be managed.

Clinical manifestation of coronavirus disease (COVID-19) varies from asymptomatic to severe clinical forms that can result in acute respiratory distress syndrome or in multiple organ dysfunction syndromes. There are no guidelines, based on randomized controlled trials, for the treatment of COVID-19 patients. The treatment is based on antiviral drugs, invasive and non-invasive ventilation supports, and anticoagulant therapy. This is a pictorial essay covering the multiple adverse events encountered during the treatment of COVID-19 patients in an area with a high pandemic incidence. Adverse events are defined as unexpected events following treatment for the infection. The cases described would be useful in aiding early diagnosis, limiting and improving the management of serious complications for patients, and allowing rapid and appropriate treatment.

Assessing the risk of malignancy in the thyroid with ultrasound (US) is crucial in patients with nodules, as it can aid in selecting those who should have a fine-needle aspiration (FNA) biopsy performed. Many studies have examined whether the US characteristics of thyroid nodules are useful indicators of histological malignancy. Overall, these investigations have identified a few US features that are significantly more frequent in malignant thyroid nodules which can be coalesced into a defining set to be used as an indicator of a higher risk of malignancy. Despite these efforts, none of these classifications have been widely adopted worldwide, and there are still conflicting recommendations from different institutions. Understanding the role and appropriate utilization of these systems could facilitate the effective interpretation and communication of thyroid US findings among referring physicians and radiologists. In this comprehensive review, we outline the major US classification systems of thyroid nodules published in the last few years.

Introduction: Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. Over the last two decades, median overall survival (OS) for patients with metastatic CRC (mCRC) has increased to roughly 30 months due to the improvements in number and efficacy of systemic therapies. Recently, two novel drugs have been approved for the treatment of chemorefractory mCRC patients such as Regorafenib and Trifluridine/Tipiracil (TAS-102). However, despite their clinical approval, it still remains unclear which of these two drugs should be used first because of lack of head-to-head randomized trials. Methods: We have compared retrospectively the safety and efficacy between regorafenib and Tas-102 in patients with mCRC refractory to standard therapies who had access to both drugs at a single institution between January 2018 and February 2019, in a clinical practice setting. The progression-free survival (PFS) and overall survival (OS) were compared using a log-rank test with 95% confidence intervals (95% CIs) Results: Forty-six patients with mCRC treated with regorafenib or TAS102, in a clinical practice setting, after failure of standard therapies including fluoropyrimidine, oxaliplatin, irinotecan, anti-VEGF therapy and anti-EGFR agents in RAS wild type were included in the analysis. In particular, among them 25 patients were treated for the first time (primary treatment) with regorafenib whereas 21 patients were treated with TAS-102. Of these patients, 20 patients switched to crossover treatment. In particular, 12 went on to receive TAS-102 and 8 went on to receive regorafenib as secondary treatment. Baseline demographic and disease characteristics were well balanced between the two groups in terms of the primary treatment. No patient had complete response (CR) or partial response (PR). The median OS was 15 months for regorafenib and 15.2 months for TAS-102 and the corresponding values after crossover were 5.4 and 5.1 months respectively. Median PFS1 defined as the interval from the first administration of the primary treatment to the first radiological progression or death from any cause, whichever come first, was 4.2 months for regorafenib and 4 months for TAS-102. However, median PFS2 defined as the interval from the initiation of secondary treatment to secondary progression, for those who had undertaken crossover treatments after first progression was 4.7 months for regorafenib and 3.3 months for TAS-102. No unexpected adverse events (AEs) were found compared with previously reported data. Moreover, AEs were tolerable even after the crossover. Conclusion: No significant difference between regorafenib and TAS-102 sequence treatments was observed in patients with mCRC. Further analyses are ongoing to potentially identify a biomarker to distinguish the two drugs.

Introduction: Tumour heterogeneity represents a possible cause of error in detecting predictive genetic alterations on tumour tissue. Liquid biopsy allows the detection of DNA alterations in circulating tumour DNA from all metastatic sites and thus overcomes the limitations of single-specimen analysis in terms of tumour heterogeneity. Methods: We assessed 45 consecutive patients with a diagnosis of metastatic colorectal cancer (mCRC) between July 2018 and February 2019 at the Oncology Unit of Università della Campania "L. Vanvitelli" using Idylla(TM) Biocartis, a fully automated real-time-PCR-based molecular diagnostic system that evaluates the most frequent mutations of KRAS, NRAS and BRAF genes. We correlated results from both liquid biopsy and standard tissue-based NGS analysis to clinical characteristics of the patients. Results: The overall agreement with the standard method was 82,2% (37/45 patients). Considering only the tests carried out before the beginning of any systemic treatment the concordance was 84,2% (16/19 patients), while, excluding patients without hepatic metastases, concordance was 92,8% (13/14 patients). Of the 3 cases of discordance at baseline, 2 were RAS/BRAF WT for liquid biopsy, while resulting KRAS and NRAS mutated on tissue analysis; whereas 1 was NRAS mutated for liquid biopsy, while resulting RAS/BRAF WT on tissue analysis. Notably, the PFS to anti-EGFR therapy in the latter case was 3 months, reflecting a primary resistance to therapy. The other 5 cases of discordance were observed in patients whose tumors were RAS/BRAF WT at baseline on tissue analysis and that resulted KRAS mutated on liquid biopsy after an anti-EGFR treatment, suggesting the emergence of RAS-mutated, resistant cancer cell clones following anti-EGFR monoclonal antibody therapy. Conclusion: Clinical practice testing of RAS/BRAF mutations using the Idylla(TM) Biocartis liquid biopsy platform is feasible and reliable in mCRC patients. The concordance at baseline is optimal when considering patients with liver metastases. In cases of RAS/BRAF WT analysis on tumour tissue specimens, liquid biopsy may better predict response to anti-EGFR agents.

Background AXL and transforming growth factor β (TGF-β) signalling pathways play a key role in modulating tumour microenvironment by promoting epithelial to mesenchymal transition (EMT), stromal activation and regulating immune response in colorectal cancer (CRC). Here we have evaluated the effect of double blockade of TGF-β and AXL receptors, as an innovative therapeutic strategy for CRC. Methods We assessed the correlation of TGF-β and AXL by an in silico analysis of a human CRC gene expression profile database. Afterwards, an evaluation of AXL expression of in a panel of human CRC cell lines by Western Blot (WB) and Real time PCR was performed. The sensitivity of HCT116 and LOVO cells to treatment with galunisertib (LY21209761), a TGF-β R1 inhibitor, and R428, an AXL inhibitor, was assessed by MTT, cell migration, and colony forming assays. Furthermore we generated patient derived 3D spheroid cultures from primary CRC, and tested their susceptibility to galunisertib and R428 by MTT assay. Finally, in vivo experiments were done with HCT116 and LOVO tumour xenografts in immunodeficient mice. Results In silico analysis showed an association between high expression levels of AXL and TGF-β R1 in CMS4 CRC. AXL was differently expressed on cell lines, and interestingly it resulted increased in HCT116 and LOVO after TGF-β inhibition, probably representing a mechanism of cancer cell escape. Dual blockade with galunisertib and R428 determined a reduction in cell migration of 50% in HCT116 and 37% in LOVO cells, respectively, and colony formation of approximately 90 % in both cell lines. Moreover, combined treatment displayed a strong synergistic activity in 3D cultures derived from five human CRC samples, resulting in the inhibition of proliferation ranging from 80 to 90%. The in vivo experiments of HCT116 and LOVO subcutaneous xenograft models are currently on going and results will be presented. Conclusions Combined TGF-β and AXL inhibition showed a promising activity in preclinical models of CRC and could represent a novel potential therapeutic strategy for patients with CRC. Legal entity responsible for the study Universita degli studi della Campania "Luigi Vanvitelli". Funding ICURE project, Universita degli studi della Campania "Luigi Vanvitelli". Disclosure D. Melisi: Research grant/Funding (self): Lilly.

To evaluate the feasibility and response to palliative radiotherapy delivered with static ports of tomotherapy--TomoDirect (TD) in patients affected with painful bone metastases from solid tumors.A prospective cohort of 130 patients (185 osseous lesions) was treated between 2010 and 2013 with TD. Three fractionation schedules were employed according to clinical decision-making (3 Gy × 10; 4 Gy × 5; 8 Gy × 1). Pain response was investigated at 2 weeks and 2 months (for evaluable patients). The Numeric Rating Scale (NRS-11) was used to assess pain. Response rates to radiotherapy were calculated following the criteria of the International Bone Metastases Consensus Group (IBMCG), accounting for the use of concomitant analgesics (response: complete or partial; non-response: stable pain, pain progression or "other"). Analgesic consumption was recalculated into the daily oral morphine-equivalent dose (OMED).Most of the patients had 1-2 bone metastases (91); those with multiple lesions mostly had a metachronous presentation (60%). Synchronous lesions were mainly approached with multiple plans (63%). Most treatments employed 3-4 fields (77%). Treatment times ranged from 255 to 939 s depending on fractionation, fields, and target lesions number. At 2 weeks, the median self-reported worst pain decreased significantly as median oral morphine-equivalent dose regardless of fractionation used. The response rate according to the IBMCG-based response categories ranged from 45 to 55%. Pain relief duration seems (response at 2 months) slightly inferior with the single fraction approach, with a higher re-treatment rate. At 2 weeks, the median self-reported worst pain and OMED significantly decreased regardless of fractionation (response rate: 49-55%). Pain relief decreased at 2 months, especially for single fraction (higher re-treatment rate).TD is a valid option to deliver palliative radiotherapy for painful bone metastases from solid tumors.

To report the 1-year outcomes of a prospective phase II study on hypofractionated whole-breast intensity-modulated radiotherapy (IM-WBRT) with a simultaneous integrated boost (SIB) to the tumor bed delivered with static ports of tomotherapy (TomoDirect) (TD).A prospective cohort of 82 patients was enrolled between 2011 and 2012. Treatment schedule consisted of 45 Gy/20 fractions to the whole breast and 50 Gy/20 fractions to the surgical bed delivered concomitantly with TD over 4 weeks. A one-armed optimal two-stage Simon's design was selected to test the hypothesis that treatment modality under investigation would decrease acute skin toxicity over historical data using conventional fractionation and sequential boost. Primary endpoint was acute skin toxicity. Secondary endpoints included late toxicity, cosmesis, quality of life and local control.Median follow-up was 12 months (range 6-18). Maximum detected acute skin toxicity was G0 41 %; G1 53 %; G2 6 %; G31 %. With two G2-G3 acute skin toxicity events in the first stage and four in the second, the study fulfilled the requirements for the definition of the treatment approach under investigation as promising. Late skin toxicity was mild with noG2 events. Cosmesis was good/excellent in 91 % of patients and fair/poor in 9 %. Quality of life was preserved over time, with the exception of fatigue, which was transiently increased.Hypofractionated IM-WBRT with a SIB to the tumor bed delivered with TD provides consistent clinical results and it is able to reduce acute skin toxicity rate over conventionally fractionated and sequential boost tomotherapy-based IM-WBRT.

The shelf life of milk and its products is strongly influenced by the quality of raw milk. Several bacteria present in raw milk can produce proteases: among them, those from psychotropic microorganisms (e.g. Bacillus subtilis), which produce enzymes under refrigeration, cause the most serious problem. The interaction of these enzymes with the milk proteins and the main proteolytic enzymes becomes important in determining the quality of the milk. An artificial substrate (azocasein) was used to quantify the enzyme activity through the release of a chromogenic product that was measured spectrophotometrically after clarifying the sample by the addition of trichloroacetic acid. The detection limit and quantification limit were 1.43 and 4.77 mg/ml respectively for sheep milk and, 2.25 and 7.5 mg/ml respectively for goat milk. This method is useful for determining the proteolytic activity in different media and its effectiveness depends on chemical-nutritional characteristics of the sample.

Radioimmunotherapy with 90Y-ibritumomab tiuxetan has been used successfully used in the treatment of CD20-positive non-Hodgkin’s lymphoma (NHL). Pretherapy imaging with 111In-ibritumomab tiuxetan has been used in provisional dosimetry studies. Posttherapy imaging of 90Y-ibritumomab tiuxetan for clinical use is appealing as it would simplify the data acquisition process and allow measurements of actual doses absorbed during treatment. The study included 29 patients with non-Hodgkin’s lymphoma, of whom 16 (group I) received a pretherapy 111In-ibritumomab tiuxetan diagnostic study and 90Y-ibritumomab tiuxetan treatment 1 week later, and 13 (group II) received only 90Y-ibritumomab tiuxetan treatment. Planar imaging and blood sampling were performed in all patients. The doses absorbed by organs at risk were calculated using a whole-body average attenuation correction factor (relative dosimetry approach) and, in the case of the 111In-ibritumomab tiuxetan image sets, also using organ-specific attenuation correction factors (absolute dosimetry method). Red marrow absorbed doses were based on gamma counting of blood samples. The estimated red marrow absorbed doses from 111In and 90Y data were equivalent. In all cases, the doses absorbed by organs at risk were found to be within prescribed limits. The relative dosimetry approach applied to both the 90Y and 111In data significantly underestimated the doses relative to those obtained with the 111In absolute dosimetry method which is generally accepted as the reference method (MIRD 16). In the case of 111In, the relative dosimetry approach values were highly correlated (R 2 = 0.61) with the reference method values. Relative dosimetry estimates may be adjusted multiplying by a correction factor of 2.8. The 90Y-ibritumomab tiuxetan relative dosimetry data correlated poorly with the reference method values (R 2 = 0.02). Based on patient-specific dosimetry, the administered activity may be increased by an average factor of 2.4, indicating that most patients could be undertreated. The relative dosimetry approach based on planar imaging largely underestimates doses relative to reference values. Dosimetry based on planar bremsstrahlung imaging is not a dependable alternative to 111In dosimetry.

This technical note describes a new robotic workstation for neurological rehabilitation, shortly named Braccio di Ferro. It has been designed by having in mind the range of forces and the frequency bandwidth that characterize the interaction between a patient and a physical therapist, as well as a number of requirements that we think are essential for allowing a natural haptic interaction: back-driveability, very low friction and inertia, mechanical robustness, the possibility to operate in different planes, and an open software environment, which allows the operator to add new functionalities and design personalized rehabilitation protocols. Braccio di Ferro is an open system and, in the spirit of open source design, is intended to foster the dissemination of robot therapy. Moreover, its combination of features is not present in commercially available systems.

"\"Markers predictive of treatment effect might be useful to improve the treatment of patients with metastatic solid tumors. Particularly, early changes in tumor metabolism measured by PET\\\/CT with F-18-FDG could predict the efficacy of treatment better than standard dimensional Response Evaluation Criteria In Solid Tumors (RECIST) response. Methods: We performed PET\\\/CT evaluation before and after 1 cycle of treatment in patients with resectable liver metastases from colorectal cancer, within a phase 2 trial of preoperative FOLFIRI plus bevacizumab. For each lesion, the maximum standardized uptake value (SUV) and the total lesion glycolysis (TLG) were determined. On the basis of previous studies, a

BACKGROUND: Baroreflex sensitivity provides useful prognostic information in patients after acute myocardial infarction. However, no data are available about the effects of converting enzyme inhibition on this variable. OBJECTIVES: The aim of the study was to evaluate the effects of angiotensin-converting enzyme inhibition on baroreflex sensitivity in patients after uncomplicated myocardial infarction. METHODS: Twenty-five patients after uncomplicated myocardial infarction underwent baroreflex sensitivity evaluation 72 to 96 h after symptom onset and after 4 days of captopril therapy. Twenty additional patients with the same characteristics were evaluated at the same time intervals before and after placebo administration to identify spontaneous baroreflex sensitivity variations. Baroreflex sensitivity was assessed by calculating the regression line relating phenylephrine-induced increases in systolic blood pressure to the attendant changes in the RR interval. RESULTS: The mean baroreflex sensitivity value increased after captopril administration from 6.5 +/- 4.2 to 11.8 +/- 6.1 ms/mm Hg (p less than 0.01) and in individual analyses increased by greater than 2 ms/mm Hg in 68% of patients. Mean plasma renin activity increased after captopril from 3.7 +/- 2.4 to 8.5 +/- 4.9 ng/ml per h (p less than 0.005). No difference was detectable in baroreflex sensitivity and plasma renin activity values according to the site of necrosis. In the control group, baroreflex sensitivity and plasma renin activity remained unchanged between the two studies. CONCLUSIONS: This study demonstrates that in patients with uncomplicated myocardial infarction, captopril significantly improves the chronotropic response to baroreceptor stimulation.

The effects of captopril and digoxin treatment on left ventricular remodeling and function after anterior myocardial infarction were evaluated in a randomized unblinded trial. Fifty-two patients with a first transmural anterior myocardial infarction and a radionuclide left ventricular ejection fraction less than 40% were randomly assigned to treatment with captopril (Group A) or digoxin (Group B). The two groups had similar baseline hemodynamic, coronary angiographic, echocardiographic and radionuclide angiographic variables. Among the 40 patients (20 in each group) who were followed up for 1 year, echocardiographic end-diastolic and end-systolic volumes were unmodified in Group A and global wall motion index was improved (p less than 0.01); in Group B, end-diastolic and end-systolic volumes increased (p less than 0.001 for both) and global wall motion index was unchanged. Rest radionuclide ejection fraction increased significantly in both groups (p less than 0.001, Group A; p less than 0.005, Group B). A comparison of the changes in the considered variables between the two groups after 1 year of treatment showed a difference in end-diastolic (p less than 0.005) end-systolic volumes (p less than 0.001) and global wall motion index (p less than 0.005) without differences in radionuclide ejection fraction, which improved to a similar degree in both groups. The results of this study suggest that captopril therapy, started 7 to 10 days after symptom onset in patients with anterior myocardial infarction and an ejection fraction less than 40%, improves both left ventricular remodeling and function and prevents left ventricular enlargement and in these patients performs better than digitalis.

We herein report on a case of synchronous bilateral breast cancer patient undergoing adjuvant intensity-modulated whole breast with static angle tomotherapy (TomoDirect). The patient was treated with a hypofractionated schedule employing a simultaneous integrated boost approach. Radiotherapy schedule was 45 Gy/20 fractions (2.25 Gy daily) to the bilateral whole breast and 50 Gy/20 fractions (2.5 Gy daily) to the 2 lumpectomy cavities. Treatment was delivered over 4 weeks. Dosimetric results were robust with consistent target coverage and adequate normal tissue avoidance. Treatment was generally well-tolerated and acute toxicity profile was mild. The present report highlights the promising clinical feasibility of TomoDirect for bilateral breast irradiation.

Besides its effects on water balance, arginine vasopressin (AVP) increases peripheral vascular resistance and decreases cardiac output, mainly by decreasing heart rate. The current study was designed to evaluate cardiac performance in patients with central diabetes insipidus (CDI), focusing on the acute effects of desmopressin replacement withdrawal and its subsequent reinstatement in patients with CDI. Twelve patients with CDI and 12 sex- and age-matched healthy subjects entered the study. All patients were receiving treatment with intranasal desmopressin at standard doses. All patients and controls were assessed for water balance, by measuring plasma osmolality and total body water, anterior pituitary function, heart rate, systolic and diastolic blood pressure. Left ventricular (LV), end-diastolic and end-systolic diameters (LVEDD, LVESD) and volumes (LVEDV, LVESD), end-diastolic and end-systolic interventricular septum thickness (EDIVST, ESIVST) and posterior wall thickness (LVEDPWT, LVESPWT), and mass (LVM) were measured by echocardiography. Moreover, LV systolic function was assessed by measuring the ejection fraction (EF), the fractional shortening (FS), the Suga index, the stroke volume and the cardiac output, while LV diastolic function was assessed by measuring early (M1) and late (M2) maximal transmitral blood flow velocities, the ratio between M1 and M2, the mitral deceleration time (MDT) and the isovolumetric relaxation time. All parameters were assessed in the patient group 24 h after discontinuing treatment with nasal desmopressin (baseline study) and 1 week after re-starting replacement treatment, while in the control group before (baseline study) and after 1-week of a nasally administered placebo. At baseline, compared to controls, patients with CDI had increased plasma osmolality (P < 0.01), plasma ACTH (P < 0.01), serum (P < 0.01) and urinary cortisol (P < 0.01) levels, and heart rate (P < 0.05), and decreased total body water (P < 0.05). Systolic and diastolic blood pressure and the other anterior pituitary hormones were similar in patients and controls. At echo-cardiography, EDIVST (P < 0.05), ESIVST (P < 0.01), LVEDPWT (P < 0.05) and LVESPWT (P < 0.01), EF (P < 0.01), Suga index (P < 0.05), FS (P < 0.05), M2 (P < 0.01) and IRT (P < 0.05) were significantly higher while LVESD (P < 0.01), LVESV (P < 0.01), LVEDD (P < 0.05), LVEDV (P < 0.05), M1 (P < 0.05), and M1/M2 (P < 0.01) were significantly lower in patients than in controls. LVM, stroke volume and cardiac output, were similar in patients and controls. In the patient group, after 1 week of replacement treatment with desmopressin, all echocardiographic parameters were normalized, except IVT, LVPWT and the diastolic parameters that were still abnormal compared to controls. No difference was found in any of the parameters in the control group one week after placebo administration. Patients with central diabetes insipidus have increased heart rate and left ventricular contractility, and impaired diastolic function. The altered heart rate and left ventricular contractility, reversible after desmopressin replacement, is likely to be due to stimulation of sympathetic nervous activity, induced by the hypovolemia associated with arginine vasopressin deficiency. Conversely, the impairment of diastolic function, persistent after desmopressin replacement, probably relates to a stable impairment of the left ventricular compliance.

To report the 2-year outcomes of whole breast intensity-modulated radiotherapy (IMRT) after conserving surgery for early breast cancer (EBC) delivered with static angle tomotherapy (TomoDirect) (TD).A prospective cohort of 120 EBC patients underwent whole breast IMRT with TD between 2010 and 2012. Radiation was delivered to a conventionally fractionated whole breast total dose of 50 Gy with TD, followed by a sequential conventionally fractionated tumor bed boost dose of 10-16 Gy with helical tomotherapy (HT). Clinical endpoints include acute and late toxicity, cosmesis, quality of life and local control.Median follow-up was 24 months (range 12-36 months); maximum detected acute skin toxicity was G0 22 %; G1 63 %; G2 12 % and G3 3 %. Predictors of acute dermatitis were as follows: volume of the whole breast minus boost volume receiving 105, 110 and 115 % of prescription dose, whole breast and boost volume, breast thickness and soft tissue thickness. Late skin toxicity was mild with noG2 events. Cosmesis was good/excellent in 91.7 % of patients and fair/poor in 8.3 %. Quality of life was preserved over time, but for fatigue, transiently increased.Adjuvant whole breast IMRT delivered sequentially with both TD and HT provides consistent clinical results. An observed unintended excessive dose outside the tumor bed might increase acute toxicity and eventually affect long-term clinical endpoints. The incorporation of the boost dose within the whole breast phase employing a simultaneous integrated boost (SIB) approach might mitigate this issue.

The present work evaluates the per-procedure, annual collective and per-capita effective doses to the Aosta Valley region population from nuclear medicine (NM) examinations performed from 2005 to 2011 at the regional NM department. Based on its demographical and socioeconomics characteristics, this area can be considered as representative of the level I countries, as defined by the United Nations Scientific Committee on the Effects of Atomic Radiation. The NM per-procedures effective doses were within the range of 0.018-35 mSv. A steady frequency per 10 000 inhabitants has been observed, together with a decrease for thyroid and whole-body bone scintigraphy. Myocardial and bone scintigraphy studies were the major contributors to the total collective effective dose. The mean annual collective and per-capita effective doses to the population were 15 man Sv y(-1) and 120 µSv y(-1), respectively. The NM contribution to the total per-capita effective dose accounts for 5.9 % of that due to the medical ionising radiation examinations overall.

Standard deviation of the histogram of left ventricular phase distribution (SDP-LV) obtained by radionclide angiography (RNA) was studied in 75 acute myocardial infarction (AMI) patients, 37 with anterior or anteroseptal (Group A) and 38 with inferior, inferolateral or posterior necrosis (Group I). In order to evaluate sensitivity, specificity and accuracy of SDP-LV compared to ejection fraction (EF) and peak filling rate (DER), 16 controls and 29 patients with coronary artery disease with normal kinesis proved by angiogaphy were studied. Patients were also compared according to normal or abnormal EF and PFR. Sensitivity of PFR was better than those of EF and PFR (86.6% vs 38.7% and 70.6%, respectively). Specificity of SDP-LV was 89.6%, better than that of PFR (58.6%), but just less than that of EF (93.1%). The accuracy of SDP-LV turned out to be better than those of EF and PFR (87.5% vs 53.8% and 67.3%, respectively). Ejection fraction correlated with SDP-LV in the total study population (r=-0.54, P

Objective. First, to test the validity of self-reported quality of care and treatment measures compared with medical records and administrative data for: eye examinations, hemoglobin A1C tests, and use of insulin and oral agents for adult patients with diabetes; and secondly to assess the consistency between medical record information and administrative data for the same measures plus microalbumin testing. Design. Cross-sectional study using data from telephone survey, primary care medical and eye records, and administrative claims. Setting. Statewide health maintenance organization in Minnesota, USA, 1995. Study participants. Four hundred and forty adults with diabetes, aged 31‐64 years. Main outcome measures. Validity of self-reported diabetes quality of care measures compared with a criterion standard combining information from primary care and eye records with information from administrative data; and reliability of medical record information compared with administrative data. Results. Although the sensitivity of self-reported eye examination was high (89%), the specificity was low (65%). Self-report of hemoglobin A1C also had high sensitivity (99%) and a lower specificity than that of eye examination (28%). The two information sources (medical records and claims) used in the criterion standard each contained complementary and nonoverlapping information. Reliability was highest for microalbumin testing (j, 0.75) and lowest for eye examination (j, 0.37). Conclusions. Quality of care measures for diabetes are often drawn from a variety of sources. To the extent that data sources are biased, the measures can be misleading. Self-report is likely to lead to an overestimate of eye screening and the measurement of hemoglobin A1C. Reported rates of quality of care should be inspected carefully. The ‘same’ rate taken from different sources may vary.

11008 Background: Early changes in tumor metabolism measured with positron-emission-tomography/computerized tomography (PET/CT) could predict the long-term efficacy of treatment better than dimensional RECIST response. Methods: We performed PET/CT before and after 1 cycle of treatment in patients with resectable liver metastases from colorectal cancer, within a phase II trial of preoperative FOLFIRI plus bevacizumab. For each lesion, the maximum SUV (SUVmax) and the total lesion glycolisis (TLG) were determined. For both, based on previous studies, a ≤-50% change from baseline was used as threshold for significant response. Metabolic response was categorized no/yes by using three different methods that enter into the calculation (i) the largest observed value (highest SUVmax/TLG), or (ii) the sum of all the observed values (Total SUVmax/TLG), or (iii) each observed values (SUVmax/TLG-by-lesion). Standard RECIST response was assessed after 3 months of treatment. The association between metabolic and RECIST response was tested with the Mc Nemar’s test and their agreement was expressed as Kappa statistics; the ability to predict progression-free (PFS) and overall (OS) survival was tested with Log-rank test and a multivariable Cox model. Results: 33 patients were analyzed. After treatment, there was a notable decrease of all PET/CT parameters, with a median change of -33.9% for the highest SUVmax, -61.5% for the highest TLG, -34.9% for the total SUVmax, and -65.5% for the total TLG. The association of SUV-based metabolic response (but not the TLG-based) with RECIST was statistically significant. However, the agreement between RECIST and PET/CT responses was consistently small. PFS and OS were significantly longer among PET/CT responding patients, whichever the measure used. On the contrary, no significant outcome difference was evident according to RECIST response. Conclusions: Early PET/CT response was significantly predictive of long-term outcomes during preoperative treatment of patients with liver metastases from colorectal cancer and its predictive ability was higher than that of RECIST response. Clinical trial information: 2006-006572-38.

e14130 Background: Irinotecan-based chemotherapy plus B was shown to be effective and safe in both first- and second-line treatment for metastatic colorectal cancer (mCRC) pts.We designed this trial to assess whether the combination of FOLFIRI + B given to untreated, potentially resectable mCRC pts was feasible and active. Methods: Phase II, single arm trial with 1-year progression-free rate (PFR) as primary end-point. A sample size of 39 pts was calculated to detect a 70% ± 12% 1-year PFR. The treatment was FOLFIRI q2w (irinotecan 180 mg/m2, leucovorin 200 mg/m2, 5FU 2400 mg/m2 iv in 46 hrs) plus B 5mg/kg q2w. Last cycle before surgery was without B. Potentially resectable, untreated mCRC pts, with liver as unique site of metastases, were eligible. Normal organ function and no contraindications to B were required. Pts were reevaluated for surgery after 6 cycles. PET-Scan were performed at baseline and at the second cycle. Results: Overall 39 pts were enrolled. Median age was 58 (range 30-75), male/female were 24/15. Twenty seven pts (69.2%; 95%CI 52.4% – 83.0%) were progression-free at 1-year. Thirty seven pts (94.9%) underwent surgery. One complete and 22 partial responses were observed (response rate 59.0%; 95% CI 42.1% – 74.4%); 5 pts had disease progression (4 resectable and 1 unresectable). Early PET-scan was assessed according PERCIST criteria [Wahl RL, J Nucl Med 2009] in 29 pts and showed metabolic response (SUV-max decrease > 30%) in 17 (58.6%; 95% CI: 38.9%- 76.5%).Severe toxicity includes grade 3 neutropenia (3 pts, 7.7%) and grade 3 diarrhea (1 pt, 2.6%). Other toxicities include grade 1-2 diarrhea (15.4%), grade 2 nausea (7.8%), grade 2 leucopenia (5.1%), grade 2 asthenia (5.1%), grade 1 anemia (2.6%), grade 2 thrombosis (2.6%). Overall, 16 pts out of 37 experienced surgical complications (43.2%; 95%CI 27.1% - 60.5%): biliary leak (11 pts, 29.7%), biliary fistula (1 pt, 2.7%), other complications (4 pts, 10.8%). All complications were reversible. No peri-operative bleeding was observed. Conclusions: The trial yielded its primary aim and shows that FOLFIRI plus B is feasible and active as neo-adjuvant treatment in patients with resectable liver metastases of CRC.

The incidence and prognostic significance of silent myocardial ischemia in 175 patients who survived a first acute myocardial infarction (AMI) were assessed by means of maximal exercise stress test and 24 hour continuous ECG monitoring performed before discharge. Thirteen patients showed silent ischemia with both techniques, 31 only with stress test, 5 only with ECG monitoring and 8 had a doubtful stress test but showed S-T segment depression during ECG monitoring, 118 were free from ischemia. Ten cardiac deaths and 31 coronary events including unstable angina, by-pass operation, and myocardial infarction occured during the one year follow-up period. S-T segment depression during ECG monitoring showed a lower sensitivity but a higher specificity and predictive accuracy for cardiac death and coronary events than did exercise stress test. When S-T segment depression is detected in the same patient with both techniques the sensitivity is lower and specificity higher. Whenever the presence of S-T segment depression is recorded, it shows a good sensitivity without significantly decreasing the specificity. Classifying patients according to the occurence of S-T segment depression on exercise test and/or ECG ambulatory monitoring, the Yates corrected chi-square test showed a significant pattern when cardiac deaths and coronary events are considered together (p< 0.01). However, the incidence of cardiac deaths and coronary events was comparable in patients with exercise S-T segment depression regardless of the occurence of S-T segment changes during continuous ECG monitoring. All 8 patients who stopped the exercise test before reaching target heart rate for dyspnea (5 patients), arrhythmias (2 patients), and hypertensive response (1 patient) had S-T segment depression during ECG monitoring: 2 of them died during follow-up and 3 suffered from unstable angina. Thus, ECG monitoring of these patients adds same helpful information but is less useful in patients who perform a maximal exercise stress test.